ABSTRACT
Objective:To evaluate the safety of ensartinib in the treatment of anaplastic lymphoma kinase (ALK) -positive non-small cell lung cancer (NSCLC) in the real-world clinical setting.Methods:Clinical data of 2 221 patients with ALK-positive locally advanced or metastatic NSCLC who received ensartinib treatment (225 mg/d) from December 16, 2020 to December 16, 2021 were collected and analyzed to assess drug adverse reactions in all population including elderly patients (≥ 65 years old) .Results:Among the total 2 221 patients, 511 patients (23.01%) experienced adverse events, including 8 patients (0.36%) who experienced serious adverse events. Adverse events led to dose modification in 67 patients (3.02%) and discontinuation in 18 patients (0.81%). The common adverse events were rash (407/2 221, 18.33%), pruritus (41/2 221, 1.85%), constipation (41/2 221, 1.85%), and facial edema (31/2 221, 1.40%). Thirty-six patients (1.62%) experienced ≥grade 3 adverse events. After symptomatic treatment of 511 patients with adverse reactions, 50 patients (9.78%) were healed, 271 patients (53.03%) were improved, 120 patients (23.48%) were persisted, and 70 patients (13.71%) were unknown due to loss of follow-up or other reasons. Forty-three patients (1.94%) reported 57 unintended adverse reactions. Among the 599 elderly patients, 116 patients (19.37%) experienced adverse events, including 1 patient (0.17%) who experienced serious adverse events. Adverse events led to dose modification in 25 patients (4.17%) and discontinuation in 5 patients (0.83%). The common adverse events of elderly patients were rash (88/599, 14.69%), constipation (14/599, 2.34%), facial edema (12/599, 2.00%), and pruritus (10/599, 1.67%). Twelve patients (2.00%) experienced ≥grade 3 adverse events. Among the 116 elderly patients with adverse reactions following the symptomatic treatment, 11 patients (9.48%) were healed, 58 patients (50.00%) were improved, 28 patients (24.13%) were persisted, and 19 patients (16.39%) were unknown due to loss of follow-up or other reasons. During the treatment, 1 patient (0.05%) experienced grade 2 interstitial lung disease, and no patient died due to adverse events.Conclusion:Ensartinib has a favorable safety profile in the real-world populations, with the most frequent adverse events being rash, mostly mild, and low incidence of ≥grade 3 adverse events. Overall, adverse reactions were tolerable and manageable.
ABSTRACT
Lung squamous cell carcinoma (LSCC) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases and is the second most common histological type of lung cancer. Anaplastic lymphoma kinase (ALK)-positive NSCLC accounts for only 2%-5% of all NSCLC cases, and is almost exclusively detected in patients with lung adenocarcinoma. Thus, ALK testing is not routinely performed in the LSCC population, and the efficacy of such treatment for ALK-rearranged LSCC remains unknown. Echinoderm microtubule associated protein like 4 (EML4)-ALK (V1) and TP53 co-mutations were identified by next generation sequencing (NGS) in this patient with advanced LSCC. On December 3, 2020, Ensatinib was taken orally and the efficacy was evaluated as partial response (PR). The progression-free survival (PFS) was 19 months. When the disease progressed, the medication was changed to Loratinib. To our knowledge, Enshatinib created the longest PFS of ALK-mutant LSCC patients treated with targeted therapy since literature review. Herein, we described one case treated by Enshatinib involving a patient with both EML4-ALK and TP53 positive LSCC, and the relevant literatures were reviewed for discussing the treatment of this rare disease. .
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/pathology , Anaplastic Lymphoma Kinase/metabolism , Carcinoma, Squamous Cell/genetics , Mutation , Cytoskeletal Proteins/genetics , Lung/pathology , Oncogene Proteins, Fusion/genetics , Protein Kinase Inhibitors/therapeutic use , Tumor Suppressor Protein p53/geneticsABSTRACT
OBJECTIVE To evaluate the econo mical efficiency of ensatinib i n the first-line treatment of anaplastic lymphoma kinase（ALK）positive-advanced non-small cell lung cancer （NSCLC），so as to provide reference for China ’s medical insurance decision-making and rational drug use in clinic. METHODS A three-state partitioned survival model was constructed from the perspective of China ’s health system ，based on the data of the international multi-center phase Ⅲ clinical trial （eXalt3 trail），with simulation time limit of 10 years，cycle period of 30 days. The economical efficiency of ensatinib was compared with that of crizotinib（standard treatment ）in the first-line treatment of ALK positive-advanced NSCLC. The incremental cost-effectiveness ratio （ICER） was calculated with quality-adjusted life years （QALYs） as utility index. The stability of basic analysis results was validated through uncertainty analysis. RESULTS The basic analysis results showed that compared with crizotinib group ， incremental cost per capita of ensatinib group was －343 370.36 yuan，incremental utility per capita was 0.76 QALYs，ICER was －454 292.25 yuan/QALY，which was far lower than the willingness-to-pay （WTP）threshold of 1 time of China ’s per capita gross domestic product （GDP，80 976 yuan）in 2021. The results of univariate sensitivity analysis showed that progression-free survival （PFS）status utility ，progression of disease （PD）status utility and subsequent treatment cost of crizotinib had a greater impact on ICER，but these parameters could not cause the reversal of basic analysis results. Probabilistic sensitivity analysis showed that with 1 time of China ’s per capita GDP in 2021 as the WTP threshold ，the probability of ensatinib group ’s treatment possessed economical efficiency was 100％. In the situational analysis ，ICER obtained by changing the ensatinib group ’s follow-up treatment regimen was －217 671.43 yuan/QALY，which was far below WTP threshold. CONCLUSIONS For Chinese patients with ALK positive-advanced NSCLC ，compared with commonly used the first-line treatment （crizotinib），ensartinib is economical and absolutely dominant.
ABSTRACT
BACKGROUND@#Anaplastic lymphoma kinase (ALK) is an important therapeutic target for advanced non-small cell lung cancer (NSCLC). In recent years, with the emergence of several ALK tyrosine kinase inhibitors (TKI), the overall survival (OS) of ALK fusion positive patients is gradually extended. This paper reports the treatment of a late stage non-small cell lung cancer (NSCLC) patient with ALK fusion positive for more than 5 years, and analyzes the treatment process and effect evaluation, so as to provide experience for the follow-up treatment of patients.@*METHODS@#The diagnosis and treatment process of a patient with advanced ALK fusion mutation positive lung cancer admitted to the third ward of Department of oncology, Chifeng hospital, Inner Mongolia on July 3, 2015 was retrospectively analyzed.@*RESULTS@#A 42 years old male patient was admitted to our department on July 3, 2015 for "intermittent cough, chest tightness for 2 months, diagnosed with lung adenocarcinoma for 1 day". Imaging examination showed a space occupying lesion in the left lower lobe of the lung, accompanied by mediastinal lymphadenopathy and left encapsulated pleural effusion. Bronchoscopic pathology showed non-small cell carcinoma, and adenocarcinoma was tentatively suggested.@*DIAGNOSIS@#left lower lobe adenocarcinoma T1bN2M1a stage IV. Fluorescence in situ hybridization (FISH) indicated the translocation of ALK (2p23) chromosome. After 2 cycles of docetaxel+cisplatin (DP) regimens chemotherapy, disease progression occurred, so we used 6 cycles of pemetrexed+carboplatin to apply combination chemotherapy, 4 cycles of pemetrexed monotherapy were used after that. The efficacy evaluation: PR. On April 9, 2016, the patient was treated with crizotinib. In August 2019, multiple intracranial metastases were found and whole brain radiotherapy was given. Since September 4, 2019, oral administration of nsatinib has been carried out. As of March 1, 2021, the patients were followed up well.@*CONCLUSIONS@#The advanced ALK fusion positive lung adenocarcinoma patients, though the first-line and the second-line chemotherapy, and the follwing application of ALK-TKI treatment, has procured a total OS has reached 68 months, and the current follow-up is good.
ABSTRACT
Lung cancer is one of the most common malignancies with the highest incidence rate and mortality rate worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85%. Only 5% NSCLC patients are anaplastic lymphoma kinase (ALK) rearrangement positive NSCLC, but the prognosis of these patients is poor, and treatment is urgent. Ensartinib (X-396), a next-generation ALK tyrosine kinase inhibitor (ALK-TKI), has shown greater potency on inhibiting ALK activity and controlling brain metastases than crizotinib, which is indicated for the treatment of crizotinib-resistant, ALK-positive NSCLC patients. Several phase I to III clinical trials included both healthy volunteers and NSCLC patients have been conducted both in China and abroad. In this review, we briefly summarized the results of these trials, and preliminary efficacy, safety, pharmacology and pharmacokinetics/pharmacodynamics of ensartinib were discussed.